JAK2 variations and functions in lung adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23181-e23181
Author(s):  
Xu Yanjun ◽  
Fan Yun
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Treatment Options ◽  
Jak2 V617f ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Pathogenesis

e23181 Background: Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains extremely low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers, including lung cancer. Recently we found that JAK2 might play an important role in lung cancer pathogenesis as an oncogene. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the activities of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients. Methods: The expression level of JAK2 mRNA was assayed using RT-PCR. JAK2 mutations and amplification were detected using next-generation sequencing (NGS). MTT assay, Transwell migration and invasion assay were conducted to study the proliferation, migration and invasion abilities of lung adenocarcinoma cells independently. The shRNA and overexpression plasmids of JAK2 were conducted. Results: JAK2 is up-regulated in lung adenocarcinoma tissues when compared with their adjacent non-tumor tissues, and was associated with lymph node metastasis ( p< 0.05). JAK2 V617F and N30S mutations and JAK2 amplification were detected by NGS in lung adenocarcinoma patient samples. Downregulation of JAK2 inhibits the proliferation, migration and invasion abilities of lung cancer cells. Moreover, overexpression of JAK2 induced the proliferation, migration and invasion abilities of lung cancer cells. Conclusions: These findings demonstrate that JAK2, whose expression is up-regulated in lung adenocarcinoma, whose mutation and amplification were detected in lung adenocarcinoma, may participate in lung cancer progression by regulating cancer cells proliferation, migration and invasion.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yu Zhong ◽  
Liting Yang ◽  
Fang Xiong ◽  
Yi He ◽  
Yanyan Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Lung Cancer Patients ◽  
Lung Cancer Metastasis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractActin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients’ poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer’s migration and invasion may provide novel therapeutic targets for lung cancer patients’ early diagnosis and therapy.

scholarly journals Quiescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer Cells Promotes Cancer Metastasis

2018 ◽  
Vol 19 (10) ◽  
pp. 3213 ◽  
Author(s):  
Hye-Jin Sung ◽  
Jung-Mo Ahn ◽  
Yeon-Hee Yoon ◽  
Sang-Su Na ◽  
Young-Jin Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Sulfhydryl Oxidase ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
Quiescin Sulfhydryl Oxidase

As lung cancer shows the highest mortality in cancer-related death, serum biomarkers are demanded for lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS–MS proteomic analysis. Quiescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the enriched proteins in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p < 0.05, Area Under curve (AUC) = 0.89) when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 were also uniquely detected in lung cancer tissues, among several other solid cancers, by immunohistochemistry. QSOX1-knock-downed Lewis lung cancer (LLC) cells were less viable from oxidative stress and reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and be involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

MiR-302a-3p, Sponged by HOXA-AS2, Suppresses Cell Proliferation and Invasion in Lung Cancer Cells

2019 ◽  
Vol 9 (12) ◽  
pp. 1644-1652
Author(s):  
Xueqin Pan ◽  
Dongchun Ma
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion

Lung cancer is one of the most common malignant cancers with a poor survival rate and high mortality worldwide. MiRNAs have been evaluated as crucial regulators of human gene expression, and exerted vital role involved in cancer progression. MiR-302a-3p was aberrant expressed in cancers that include pancreatic cancer and hepatocellular cancer, but its biological role in lung cancer remains elusive. This study aimed to discover the role and potential mechanism of miR-302a-3p in lung cancer. The lung cancer cell line with the highest expression of miR-302a-3p was selected, which was then subjected to transfection of miR-302a-3p mimic. Quantitative RT-PCR was performed to detect gene expression. Western blot assay was performed to determine corresponding genes that related to cell proliferation, apoptosis and invasion. Cell Counting Kit (CCK)-8 assay, flow cytometry analysis, wound healing and Transwell assay were performed to detect cell proliferation, apoptosis, migration and invasion, respectively. Luciferase reporter assay was carried out to identify the targeting relationship of miR-302-3p and HOXA-AS2. MiR-302a-3p was downregulated in lung cancer cells, and overexpression of miR-302a-3p significantly suppressed cell proliferation, migration, invasion and promoted cell apoptosis. HOXA-AS2 was a direct target of miR-302a-3p and was regulated by miR-302a-3p. HOXA-AS2 was upregulated in lung cancer cells. Upregulated HOXA-AS2 could reverse the effect that overexpression of miR-302a-3p caused on cell proliferation, apoptosis, migration and invasion. Overall, miR-302a-3p exhibited anti-oncogenic activity by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis in lung cancer by targeting HOXA-AS2, disclosing the role and regulatory mechanism of miR-302a-3p, which provided a promising therapeutic target for the clinical application of lung cancer treatment.

Quescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer cells Promotes Cancer Metastasis

2018 ◽  
Author(s):  
Hye-Jin Sung ◽  
Jung-Mo Ahn ◽  
Yeon-Hee Yoon ◽  
Sang-su Na ◽  
Young-Jin Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Sulfhydryl Oxidase ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Cancer Tissues

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p&lt;0.05, AUC=0.89), when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

scholarly journals Quescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer Cells Promotes Cancer Metastasis

2018 ◽  
Author(s):  
Hye-Jin Sung ◽  
Jung-Mo Ahn ◽  
Yeon-Hee Yoon ◽  
Sang-su Na ◽  
Young-Jin Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Sulfhydryl Oxidase ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Cancer Tissues

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p&lt;0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

scholarly journals CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4057
Author(s):  
Yen-Yun Wang ◽  
Anupama Vadhan ◽  
Ping-Ho Chen ◽  
Yen-Lung Lee ◽  
Chih-Yeh Chao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Nodes ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Cancer Stemness ◽  
Primary Tumors

Lung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understanding the molecular pathogenesis behind cancer-stemness-mediated metastasis and developing effective approaches to prevent metastasis are key issues for improving cancer treatment. In this study, we investigated the role of CD44 stemness marker in lung cancer using in vitro and clinical studies. Immunohistochemical staining of lung cancer tissue specimens revealed that primary tumors with higher CD44 expression showed increased metastasis to regional lymph nodes. Flow cytometry analysis suggested that CD44 positive cells were enriched in the metastatic lymph nodes compared to the primary tumors. CD44 overexpression significantly increased migration and invasion abilities of lung cancer cells through CD44-induced ERK phosphorylation, ZEB1 upregulation, and Claudin-1 downregulation. Furthermore, ERK inhibition suppressed the migration and invasion abilities of CD44-overexpressing lung cancer cells. In summary, our in vitro and clinical results indicate that CD44 may be a potential prognostic and therapeutic marker for lung cancer patients.

scholarly journals ONECUT2 overexpression promotes RAS-driven lung adenocarcinoma progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Qingyang Ma ◽  
Kai Wu ◽  
Hui Li ◽  
Huichun Li ◽  
Yufei Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Specific Gene ◽  
Polycomb Repressive Complex 2 ◽  
Ectopic Activation

AbstractAberrant differentiation, driven by activation of normally silent tissue-specific genes, results in a switch of cell identity and often leads to cancer progression. The underlying genetic and epigenetic events are largely unexplored. Here, we report ectopic activation of the hepatobiliary-, intestinal- and neural-specific gene one cut homeobox 2 (ONECUT2) in various subtypes of lung cancer. ONECUT2 expression was associated with poor prognosis of RAS-driven lung adenocarcinoma. ONECUT2 overexpression promoted the malignant growth and invasion of A549 lung cancer cells in vitro, as well as xenograft tumorigenesis and bone metastases of these cells in vivo. Integrative transcriptomics and epigenomics analyses suggested that ONECUT2 promoted the trans-differentiation of lung cancer cells by preferentially targeting and regulating the activity of bivalent chromatin domains through modulating Polycomb Repressive Complex 2 (PRC2) occupancy. Our findings demonstrate that ONECUT2 is a lineage-specific and context-dependent oncogene in lung adenocarcinoma and suggest that ONECUT2 is a potential therapeutic target for these tumors.

Mogroside V Inhibits Hyperglycemia-induced Lung Cancer Cells Metastasis through Reversing EMT and Damaging Cytoskeleton

2019 ◽  
Vol 19 (11) ◽  
pp. 885-895
Author(s):  
Jun Chen ◽  
Demin Jiao ◽  
Yu Li ◽  
Chunyan Jiang ◽  
Xiali Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Rho Gtpase ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: Diabetes Mellitus (DM) accelerates progress of lung cancer. Hyperglycemia, a critical feature of DM, promotes lung cancer metastasis. Mogroside V is a triterpenoid glycoside from Siraitia grosvenorii. Interestingly, mogroside V not only plays an anti-diabetic role, but also has anti-tumor effects. Objective: In this study, we investigated the metastatic efficiency of mogroside V in lung cancer cells cultured in hyperglycemia. Methods: Two lung cancer cell lines-A549 and H1299 were cultured in normoglycemia (5.5mM glucose) and hyperglycemia (25mM glucose). Cellular proliferation was tested by MTT, invasion was examined by transwell assay, migration was measured by wound healing assay, cytoskeleton was stained by Phalloidin-TRITC and the expressions of EMT markers and Rho-GTPase family protein were detected by western blot. Results: Hyperglycemia promoted the invasion and migration of A549 and H1299 cells compared with normoglycemia. Mogroside V inhibited the hyperglycemia-induced invasion and migration. Hyperglycemia promoted epithelial-mesenchymal transition (EMT), while mogroside V could reverse this process through up-regulating E-Cadherin expression and down-regulating N-Cadherin, Vimentin, Snail expressions. Furthermore, mogroside V fractured microfilaments and reduced Rho A, Rac1, Cdc42 and p-PAK1 expressions under hyperglycemic conditions. Conclusion: These results suggest that mogroside V inhibits hyperglycemia-induced lung cancer cells migration and invasion through reversing EMT and damaging cytoskeleton.

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